Johns Hopkins scientists and collaborators have identified a molecular marker called "Mig6" (mitogen-inducible gene 6) that appears to accurately predict longer survival -- up to two years -- among patients prescribed two of the most widely used drugs in a class of anticancer agents called EGFR inhibitors. The U.S. Food and Drug Administration-approved drugs, gefitinib (Iressa) and erlotinib (Tarceva), are prescribed for lung and pancreatic cancer patients, but only a few who have mutations in the EGFR gene usually benefit with a prolonged reduction of tumor size. The two drugs block the gene's ramped-up protein production, but patients' responses to the drug vary widely – from no survival benefit to several years. The average is several months. "Clinicians have had no reliable method for distinguishing patients who are not likely to respond to EGFR inhibitors and those who will respond very well," says David Sidransky, M.D., professor of otolaryngology, oncology, pathology, urology, and genetics at Johns Hopkins. Looking at the precise level of protein production from the EGFR gene alone in specific patients was not proven to be a good indicator of patients' response to EGFR-blocking drugs, but the presence or absence of Mig6 might be, he adds. In a preliminary study,publishe on July 31, 2013 in the online open-access journal, PLOS ONE, the Johns Hopkins scientists found the genetic marker in a series of experiments that began with laboratory-derived lung and head and neck cancer cell lines resistant to EGFR-inhibitor drugs. In the cell lines, the team found very high levels of protein production from the Mig6 gene -- up to three times the level in sensitive cell lines. Mig6 is one of the molecules that controls the activity of the EGFR protein.

A new research study has revealed that the cheetah, the world’s fastest land animal, matches and may even anticipate the escape tactics of different prey when hunting, rather than just relying on its speed and agility as previously thought. The study, which has just been published in the Royal Society Journal Biology Letters was carried out by a team of researchers from Queen’s University Belfast, in collaboration with other institutions in the UK (University of Aberdeen, University of Swansea, Institute of Zoology, Zoological Society of London, University of Oxford), and elsewhere (North Carolina State University, The Lewis Foundation, South African National Parks, Earth and OCEAN Technologies, Kiel, Germany). The research team used GPS and accelerometer data loggers deployed on cheetahs, along with traditional observation methods. The study was funded by a Royal Society International Joint Project grant, a NERC New Investigator award and the Lewis Foundation. Explaining the team’s findings, lead researcher Dr Michael Scantlebury, from the School of Biological Sciences at Queen’s University Belfast, said: “The more we understand about the physiology and the hunting tactics of this charismatic animal, the more we are able to ensure its continuing existence. Our study found that whilst cheetahs are capable of running at exceptionally high speeds, the common adage that they simply ‘outrun’ their prey does not explain how they are able to capture more agile animals. Previous research has highlighted their incredible speed and acceleration and their ability to turn after escaping prey. We have now shown that hunt tactics are prey-specific. In other words, we now know that rather than a simple maximum speed chase, cheetahs first accelerate towards their quarry before slowing down to mirror prey-specific escaping tactics.

Sylvia Hoff, a graduate student from the Spemann Graduate School of Biology and Medicine (SGBM), has identified a new gene that causes cystic kidneys in children and young adults. The work by the Ph.D. student Hoff and her international collaboration of partners was published in the August 2013 issue of Nature Genetics. The research group’s results lead to the identification of novel insights into the molecular mechanism underlying nephronophthisis (NPH), which is a prerequisite for developing pharmacological targets and new therapies for children with NPH. NPH is the most common inherited kidney disease that leads to renal failure in children. It is an autosomal recessive disease. The kidneys of affected children develop cysts, and as there is no approved therapy yet, patients need dialysis and renal transplantation. In addition, NPH often affects other organs apart from the kidney, such as the eyes, the liver, or the brain. Hoff, together with Dr. Soeren Lienkamp of the Nephrology Department at the Freiburg University Medical Center headed by Professor Gerd Walz, analyzed the function of NPH proteins during early developmental processes. They found that the ANKS6 protein has functions similar to those of some of the known NPH proteins. In collaboration with research groups in France, USA, Denmark, Switzerland, Egypt, the Netherlands, and Germany, they succeeded in identifying mutations in the ANKS6 gene of children with NPH. This confirmed that ANKS6 is a novel NPH-disease gene. The patients suffered from early-onset cystic kidney disease and structural heart abnormalities. Further analysis revealed that ANKS6 also forms a protein network with three other NPH proteins (INVS, NPHP3, and NEK8) at the cilium, a hair-like structure on the surface of many cells.